The long-term objective of this laboratory is to provide an understanding of how the primate brainstem controls the rapid movements of the eyes known as saccades. The proposed experiments will focus on the central Mesencephalic Reticular Formation (cMRF), an area just lateral to the oculomotor nuclei, which has been shown to participate in the generation of saccades. Removal of the CMRF in monkeys is detrimental to the initiation and performance of saccades made in response to visual stimuli. The CMRF has reciprocal anatomic connections with two other regions which directly participate in the control of saccades: the paramedian zone of the pontine reticular formation (PPRF) and the superior colliculus (SC). Previous work has hypothesized that CMRF activity may either trigger saccades or provide temporal information to the PPRF about the amplitude of the horizontal component of the upcoming saccade. This proposal is designed to test an alternative hypothesis that the CMRF may provide feedback about current change in eye position from cells in the PPRF to those in the SC. Three experimental objectives are envisioned: 1) Characterize the anatomic organization and physiologic function of cells in the CMRF related to the generation of saccades. Extracellular recordings of CMRF neurons will be made while monkeys perform a wide variety of oculomotor behaviors including responses to visual stimuli; spontaneous, visual and memory guided saccades; and periods of fixation with and without visible targets. Placement of small marking lesions at sites of cells related to small and large saccades will provide insight into whether there is a dorsal-to-ventral organization of the cell activity with respect to the amplitude of the horizontal component of saccades. 2) Determine if the cells in the CMRF are part of the control loop located within the brainstem which governs the dynamic characteristics and accuracy of saccades. Microstimulation within the CMRF for brief periods during visually and memory guided saccades will be used to assess whether activation of the CMRF (thereby increasing feedback) might terminate saccades early, making them hypometric. Another approach will record CMRF neurons during eye movements perturbed by stimulating the rostral pole of the SC. If the CMRF is within the feedback path, then the discharge of CMRF neurons should reflect the compensatory aspects of saccade perturbations. A more sophisticated approach will isolate the role the cells of the CMRF play in the control of saccades without the confounding effect of stimulating or suppressing axons en passage from the SC which course through the CMRF. Small quantities of a GABA agonist (muscimol) and a GABA antagonist (bicuculline) will be pressure injected into the CMRF. Saccade perturbations (secondary to reversible lesioning or stimulation) should reveal the physiologic role of CMRF neurons. 3) Antidromic stimulation will be used to characterize the neuronal message sent from the CMRF to two of its major efferent targets, the SC and the PPRF. The principles of organization and control of motor function revealed by these experiments may also provide insight into human neurologic disease.